Modulatory Effects of a Novel Cyclized Peptide in Reducing the Expression of Markers Linked to Alzheimer's Disease

Bibliographic Details
Title: Modulatory Effects of a Novel Cyclized Peptide in Reducing the Expression of Markers Linked to Alzheimer's Disease
Authors: Emanuele Brai, Florian Simon, Antonella Cogoni, Susan A. Greenfield
Source: Frontiers in Neuroscience, Vol 12 (2018)
Publisher Information: Frontiers Media S.A., 2018.
Publication Year: 2018
Collection: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
Subject Terms: neurodegeneration, Alzheimer's disease, ex vivo brain slices, basal forebrain, AChE-derived peptides, α7 nicotinic receptor, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
More Details: Despite many studies attempt to identify the primary mechanisms underlying neurodegeneration in Alzheimer's disease (AD), the key events still remain elusive. We have previously shown that a peptide cleaved from the acetylcholinesterase (AChE) C-terminus (T14) can play a pivotal role as a signaling molecule in neurodegeneration, via its interaction with the α7 nicotinic acetylcholine receptor. The main goal of this study is to determine whether a cyclized variant (NBP14) of the toxic AChE-derived peptide can antagonize the effects of its linear counterpart, T14, in modulating well-known markers linked to neurodegeneration. We investigate this hypothesis applying NBP14 on ex-vivo rat brain slices containing the basal forebrain. Western blot analysis revealed an inhibitory action of NBP14 on naturally occurring T14 peptide, as well as on endogenous amyloid beta, whereas the expression of the nicotinic receptor and phosphorylated Tau was relatively unaffected. These results further confirm the neurotoxic properties of the AChE-peptide and show for the first time in an ex-vivo preparation the possible neuroprotective activity of NBP14, over a protracted period of hours, indicating that T14 pathway may offer a new prospect for therapeutic intervention in AD pathobiology.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1662-453X
Relation: https://www.frontiersin.org/article/10.3389/fnins.2018.00362/full; https://doaj.org/toc/1662-453X
DOI: 10.3389/fnins.2018.00362
Access URL: https://doaj.org/article/9dd2131dc55d46e6b1a2f7b35e7a993a
Accession Number: edsdoj.9dd2131dc55d46e6b1a2f7b35e7a993a
Database: Directory of Open Access Journals
More Details
ISSN:1662453X
DOI:10.3389/fnins.2018.00362
Published in:Frontiers in Neuroscience
Language:English